Rice tillering,a key architecture trait determ ining grain yield,is highly regulated by a class of newly identified phytohorm ones,strigolactones(SLs).How ever,the whole SL signaling pathw ay from the receptor to dow ...Rice tillering,a key architecture trait determ ining grain yield,is highly regulated by a class of newly identified phytohorm ones,strigolactones(SLs).How ever,the whole SL signaling pathw ay from the receptor to dow nstream transcription factors to finally inhibit tillering remains unrevealed.In this study,we first found that brassinosteroids(BRs)strongly enhance tillering by prom oting bud outgrow th in rice,which is largely different from the function of BRs in Arabidopsis.Genetic and biochem ical analyses indicated that both the SL and BR signaling pathw ays control rice tillering by regulating the stability of D53 and/or the OsBZR1 RLA1-DLT module,a transcriptional complex in the rice BR signaling pathway.We further found that D53 interacts with OsBZR1 to inhibit the expression of FC1,a local inhibitor of tillering,and that this inhibition depends on direct DNA binding by OsBZR1,which recruits D53 to the FC1 promoter in rice buds.Taken together,these findings uncover a mechanism illustrating how SLs and BRs coordinately regulate rice tillering via the early responsive gene FC1.展开更多
Background:Abnormal aggregation of brainα-synuclein is a central step in the pathogenesis of Parkinson’s disease(PD),thus,it is reliable to promote the clearance ofα-synuclein to prevent and treat PD.Recent studies...Background:Abnormal aggregation of brainα-synuclein is a central step in the pathogenesis of Parkinson’s disease(PD),thus,it is reliable to promote the clearance ofα-synuclein to prevent and treat PD.Recent studies have revealed an essential role of glymphatic system and meningeal lymphatic vessels in the clearance of brain macromolecules,however,their pathophysiological aspects remain elusive.Method:Meningeal lymphatic drainage of 18-week-old A53T mice was blocked via ligating the deep cervical lymph nodes.Six weeks later,glymphatic functions and PD-like phenotypes were systemically analyzed.Results:Glymphatic influx of cerebrospinal fluid tracer was reduced in A53T mice,accompanied with perivascular aggregation ofα-synuclein and impaired polarization of aquaporin 4 expression in substantia nigra.Cervical lymphatic ligation aggravated glymphatic dysfunction of A53T mice,causing more severe accumulation ofα-synuclein,glial activation,inflammation,dopaminergic neuronal loss and motor deficits.Conclusion:The results suggest that brain lymphatic clearance dysfunction may be an aggravating factor in PD pathology.展开更多
The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae（Gegen）,salvia miltiorrhiza（Danshen）,radix curcuma（Jianghuang）,hawthorn（Shanzha）,salvia chinensis（Shijianchuan）,sinapis alba（Baiji...The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae（Gegen）,salvia miltiorrhiza（Danshen）,radix curcuma（Jianghuang）,hawthorn（Shanzha）,salvia chinensis（Shijianchuan）,sinapis alba（Baijiezi）,astragalus（Huangqi）,panax japonicas（Zhujieshen）,atractylodes macrocephala koidz（Baizhu）,radix paeoniae alba（Baishao）,bupleurum（Chaihu）,chrysanthemum（Juhua）,rhizoma cyperi（Xiangfu） and gastrodin（Tianma）,whose aqueous extract was fermented with lactobacillus,bacillus aceticus and saccharomycetes.ShuanTong-Ling is a formula used to treat brain diseases including ischemic stroke,migraine,and vascular dementia.Shuan-Tong-Ling attenuated H_2O_2-induced oxidative stress in rat microvascular endothelial cells.However,the potential mechanism involved in these effects is poorly understood.Rats were intragastrically treated with 5.7 or 17.2 m L/kg Shuan-Tong-Ling for 7 days before middle cerebral artery occlusion was induced.The results indicated Shuan-Tong-Ling had a cerebral protective effect by reducing infarct volume and increasing neurological scores.Shuan-Tong-Ling also decreased tumor necrosis factor-α and interleukin-1β levels in the hippocampus on the ischemic side.In addition,Shuan-Tong-Ling upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of acetylated-protein 53 and Bax.Injection of 5 mg/kg silent information regulator 1（SIRT1） inhibitor EX527 into the subarachnoid space once every 2 days,four times,reversed the above changes.These results demonstrate that Shuan-Tong-Ling might benefit cerebral ischemia/reperfusion injury by reducing inflammation and apoptosis through activation of the SIRT1 signaling pathway.展开更多
AIM To study the significance of p53 gene in hepatocarcinogenesis through analyzing codon 249 mutations of p53 gene in non neoplastic liver tissues. METHODS Codon 249 mutation was detected using single st...AIM To study the significance of p53 gene in hepatocarcinogenesis through analyzing codon 249 mutations of p53 gene in non neoplastic liver tissues. METHODS Codon 249 mutation was detected using single stranded conformational polymorphism analysis and allele specific PCR in liver tissues from 10 cases of chronic hepatitis, 5 cases of cirrhosis and 20 cases of HCCs. RESULTS The detection rate of codon 249 mutation in chronic hepatitis, cirrhosis and pericancerous tissues was 70% (7/10), 100% (5/5) and 70% (14/20), respectively by AS PCR. These mutations could not be detected by SSCP analysis. The detection rates were 65% (13/20) and 45% (9/20) in cancerous tissues by AS PCR and SSCP analysis. CONCLUSION Codon 249 mutations of p53 gene were very popular in non neoplastic liver tissues though the number of those mutant cells was only in subsection. Those mutations in cancerous tissues might take place in the stage before the formation of tumor.展开更多
Gynostemma(G.) pentaphyllum(Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum(GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal...Gynostemma(G.) pentaphyllum(Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum(GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal models of Parkinson’s disease(PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-and 6-hydroxydopamine. PD patients exhibit multiple symptoms, so PD-related research should combine neurotoxin models with genetic models. In the present study, we investigated the ameliorative effects of GP-EX, including gypenosides, on the cell death of dopaminergic neurons in the midbrain of A53 T α-synuclein transgenic mouse models of PD(A53 T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53 T mice for 20 weeks.α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53 T mice, which was reduced following treatment with GP-EX. Treatment with GP-EX modulated the reduced phosphorylation of tyrosine hydroxylase, extracellular signal-regulated kinase(ERK1/2), Bcl-2-associated death promoter(Bad) at Ser112, and c-Jun N-terminal kinase(JNK1/2) due to α-synuclein overexpression. In the A53 T group, GP-EX treatment prolonged the latency of the step-through passive avoidance test and shortened the transfer latency of the elevated plus maze test. Gypenosides treatment exhibited the effects and efficacy similar to those of GP-EX. Taken together, GP-EX, including gypenosides, has ameliorative effects on dopaminergic neuronal cell death due to the overexpression of α-synuclein by modulating ERK1/2, Bad at Ser112, and JNK1/2 signaling in the midbrain of A53 T mouse model of PD. Further studies are needed to investigate GP-EX as a treatment for neurodegenerative synucleinopathies, including PD. This study was approved by the Animal Ethics Committee of Chungbuk National University(approval No. CBNUA-956-16-01) on September 21, 2016.展开更多
Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson＇s disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY ...Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson＇s disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed： a control group （without any treatment）, a genistein group （incubated with 20 μM genistein）, a rote- none group （treated with 50 μM rotenone）, and a rotenone ＋ genistein group （incubated with 20 μM genistein and then treated with 50μM rotenone）. A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin ! levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SYSY cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein ＋ rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers （ICI-182780 and ML385, respectively）, genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson＇s dis- ease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.展开更多
In this study,a continuous-flow procedure containing four steps has been developed to synthesize Pigment Red 53 and modify its crystal structure.This process avoided the problems of conveying highly insoluble reaction...In this study,a continuous-flow procedure containing four steps has been developed to synthesize Pigment Red 53 and modify its crystal structure.This process avoided the problems of conveying highly insoluble reaction intermediates by removing intermediate operating steps.After optimization,the overall yield of Pigment Red 53:1 reached 97.1%in the total residence time of 80 s by this diazotizationcoupling-laking-crystal transition process.From batch to continuous flow,the purity of products increased from 97.1%to 98.2%and the median diameter of pigment particles decreased from 14μm to 1.9μm.This process achieved a similar crystal transition effect in 18 s as in batch,producingα,δandνcrystals of Pigment Red 53:2 as expected.In conclusion,this continuous-flow procedure displays advantages in both synthesis and crystal transition,indicating another potential use for industrial application.展开更多
基金This work was supported by grants from NNSFC(31430046 to X.W.),NKRDP(2016YFD0100403 to S.S.,2016YFD0100700 to Z.F.),ICPNNSFC(31661143024 to X.W.),MAITP(0120150092 to X.W.)School Independent Scientific and Technological Innovation Foundation and Research Startup Foundation of Huazhong Agricultural University(2662015PY020,2014RC002 to X.W.).
文摘Rice tillering,a key architecture trait determ ining grain yield,is highly regulated by a class of newly identified phytohorm ones,strigolactones(SLs).How ever,the whole SL signaling pathw ay from the receptor to dow nstream transcription factors to finally inhibit tillering remains unrevealed.In this study,we first found that brassinosteroids(BRs)strongly enhance tillering by prom oting bud outgrow th in rice,which is largely different from the function of BRs in Arabidopsis.Genetic and biochem ical analyses indicated that both the SL and BR signaling pathw ays control rice tillering by regulating the stability of D53 and/or the OsBZR1 RLA1-DLT module,a transcriptional complex in the rice BR signaling pathway.We further found that D53 interacts with OsBZR1 to inhibit the expression of FC1,a local inhibitor of tillering,and that this inhibition depends on direct DNA binding by OsBZR1,which recruits D53 to the FC1 promoter in rice buds.Taken together,these findings uncover a mechanism illustrating how SLs and BRs coordinately regulate rice tillering via the early responsive gene FC1.
基金This work was supported by grants from the National Natural Science Foundation of China(81671070 and 81473196).
文摘Background:Abnormal aggregation of brainα-synuclein is a central step in the pathogenesis of Parkinson’s disease(PD),thus,it is reliable to promote the clearance ofα-synuclein to prevent and treat PD.Recent studies have revealed an essential role of glymphatic system and meningeal lymphatic vessels in the clearance of brain macromolecules,however,their pathophysiological aspects remain elusive.Method:Meningeal lymphatic drainage of 18-week-old A53T mice was blocked via ligating the deep cervical lymph nodes.Six weeks later,glymphatic functions and PD-like phenotypes were systemically analyzed.Results:Glymphatic influx of cerebrospinal fluid tracer was reduced in A53T mice,accompanied with perivascular aggregation ofα-synuclein and impaired polarization of aquaporin 4 expression in substantia nigra.Cervical lymphatic ligation aggravated glymphatic dysfunction of A53T mice,causing more severe accumulation ofα-synuclein,glial activation,inflammation,dopaminergic neuronal loss and motor deficits.Conclusion:The results suggest that brain lymphatic clearance dysfunction may be an aggravating factor in PD pathology.
基金supported by the National Natural Science Foundation of China,No.81202625Open Fund of Key Laboratory of Cardiovascular and Cerebrovascular Diseases Translational Medicine of China Three Gorges University of China,No.2016xnxg101
文摘The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae（Gegen）,salvia miltiorrhiza（Danshen）,radix curcuma（Jianghuang）,hawthorn（Shanzha）,salvia chinensis（Shijianchuan）,sinapis alba（Baijiezi）,astragalus（Huangqi）,panax japonicas（Zhujieshen）,atractylodes macrocephala koidz（Baizhu）,radix paeoniae alba（Baishao）,bupleurum（Chaihu）,chrysanthemum（Juhua）,rhizoma cyperi（Xiangfu） and gastrodin（Tianma）,whose aqueous extract was fermented with lactobacillus,bacillus aceticus and saccharomycetes.ShuanTong-Ling is a formula used to treat brain diseases including ischemic stroke,migraine,and vascular dementia.Shuan-Tong-Ling attenuated H_2O_2-induced oxidative stress in rat microvascular endothelial cells.However,the potential mechanism involved in these effects is poorly understood.Rats were intragastrically treated with 5.7 or 17.2 m L/kg Shuan-Tong-Ling for 7 days before middle cerebral artery occlusion was induced.The results indicated Shuan-Tong-Ling had a cerebral protective effect by reducing infarct volume and increasing neurological scores.Shuan-Tong-Ling also decreased tumor necrosis factor-α and interleukin-1β levels in the hippocampus on the ischemic side.In addition,Shuan-Tong-Ling upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of acetylated-protein 53 and Bax.Injection of 5 mg/kg silent information regulator 1（SIRT1） inhibitor EX527 into the subarachnoid space once every 2 days,four times,reversed the above changes.These results demonstrate that Shuan-Tong-Ling might benefit cerebral ischemia/reperfusion injury by reducing inflammation and apoptosis through activation of the SIRT1 signaling pathway.
文摘AIM To study the significance of p53 gene in hepatocarcinogenesis through analyzing codon 249 mutations of p53 gene in non neoplastic liver tissues. METHODS Codon 249 mutation was detected using single stranded conformational polymorphism analysis and allele specific PCR in liver tissues from 10 cases of chronic hepatitis, 5 cases of cirrhosis and 20 cases of HCCs. RESULTS The detection rate of codon 249 mutation in chronic hepatitis, cirrhosis and pericancerous tissues was 70% (7/10), 100% (5/5) and 70% (14/20), respectively by AS PCR. These mutations could not be detected by SSCP analysis. The detection rates were 65% (13/20) and 45% (9/20) in cancerous tissues by AS PCR and SSCP analysis. CONCLUSION Codon 249 mutations of p53 gene were very popular in non neoplastic liver tissues though the number of those mutant cells was only in subsection. Those mutations in cancerous tissues might take place in the stage before the formation of tumor.
基金supported by the National Research Foundation of Korea,grant No.2016R1D1A3B03930722(to MKL),Republic of Korea
文摘Gynostemma(G.) pentaphyllum(Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum(GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal models of Parkinson’s disease(PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-and 6-hydroxydopamine. PD patients exhibit multiple symptoms, so PD-related research should combine neurotoxin models with genetic models. In the present study, we investigated the ameliorative effects of GP-EX, including gypenosides, on the cell death of dopaminergic neurons in the midbrain of A53 T α-synuclein transgenic mouse models of PD(A53 T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53 T mice for 20 weeks.α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53 T mice, which was reduced following treatment with GP-EX. Treatment with GP-EX modulated the reduced phosphorylation of tyrosine hydroxylase, extracellular signal-regulated kinase(ERK1/2), Bcl-2-associated death promoter(Bad) at Ser112, and c-Jun N-terminal kinase(JNK1/2) due to α-synuclein overexpression. In the A53 T group, GP-EX treatment prolonged the latency of the step-through passive avoidance test and shortened the transfer latency of the elevated plus maze test. Gypenosides treatment exhibited the effects and efficacy similar to those of GP-EX. Taken together, GP-EX, including gypenosides, has ameliorative effects on dopaminergic neuronal cell death due to the overexpression of α-synuclein by modulating ERK1/2, Bad at Ser112, and JNK1/2 signaling in the midbrain of A53 T mouse model of PD. Further studies are needed to investigate GP-EX as a treatment for neurodegenerative synucleinopathies, including PD. This study was approved by the Animal Ethics Committee of Chungbuk National University(approval No. CBNUA-956-16-01) on September 21, 2016.
基金supported by a grant from the National Key Research and Development Plan of China,No.2016YFC1101500the National Natural Science Foundation of China,No.11672332,11102235,8167050417+1 种基金the Key Science and Technology Support Foundation of Tianjin City of China,No.17YFZCSY00620the Natural Science Foundation of Tianjin City of China,No.15JCYBJC28600,17JCZDJC35400
文摘Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson＇s disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed： a control group （without any treatment）, a genistein group （incubated with 20 μM genistein）, a rote- none group （treated with 50 μM rotenone）, and a rotenone ＋ genistein group （incubated with 20 μM genistein and then treated with 50μM rotenone）. A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin ! levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SYSY cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein ＋ rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers （ICI-182780 and ML385, respectively）, genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson＇s dis- ease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.
基金financial support from Shanghai Municipal Science and Technology Commission (No.21520761100)the Open Project of State Key Laboratory of Chemical Engineering (No. SKL-Ch E-21C07)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Program of Leading Talents (2013)
文摘In this study,a continuous-flow procedure containing four steps has been developed to synthesize Pigment Red 53 and modify its crystal structure.This process avoided the problems of conveying highly insoluble reaction intermediates by removing intermediate operating steps.After optimization,the overall yield of Pigment Red 53:1 reached 97.1%in the total residence time of 80 s by this diazotizationcoupling-laking-crystal transition process.From batch to continuous flow,the purity of products increased from 97.1%to 98.2%and the median diameter of pigment particles decreased from 14μm to 1.9μm.This process achieved a similar crystal transition effect in 18 s as in batch,producingα,δandνcrystals of Pigment Red 53:2 as expected.In conclusion,this continuous-flow procedure displays advantages in both synthesis and crystal transition,indicating another potential use for industrial application.
